When growth factors cause cells to proliferate, the earliest signal is usually an increase in cytosolic calcium and pH. The increase in calcium lasts for seconds to minutes. However, there are exceptions. Some cells which proliferate in response to EGF or to insulin are characterized only by phosphorylation of tyrosines and not by a calcium signal. Smooth muscle cell contraction is also usually initiated by an increase in cytosolic calcium, which may be transient or sustained. An exception is the slow increase in contraction in response to phorbol esters. Several groups, including our own, have noted that vasoconstricting agents tend to act as weak mitogens, whereas some vasodilating drugs, including calcium antagonists, inhibit growth at least at high dose. Conversely, there is a recent report of vasoconstrictive activity of EGF, PDGF, and basic FGF. These intriguing connections between cell contraction and cell proliferation may have some relevance to the clinical situations where growth and contraction (or tension) are associated such as hypertension and hypertrophy. Because we have found basic FGF in cultured endothelial and smooth muscle cells and because an increase in cytosolic calcium has been noted with FGF administration in several cells types, such as endotbelial cells and some fibroblasts, we anticipated that it would cause an early calcium signal in cultured smooth muscle cells. However, we found no such signal. We did see an increase to 170 nM (from 100 nM baseline) some time between 12 and 24 hours after bFGF was added. This is an average value in a suspension of cells, and so could indicate each cell developed a modest increase, or that the mean was weighted by an increase in the number of cells in M phase, which is characterized by calcium transients. Studies are in progress to distinguish between these possibilities. In addition, these studies are being repeated with freshly enzyme- dispersed cells which, in contrast to passaged cells or explant- cultured cells, retain their ability to contract.